Psychotropic drugs upregulate aquaporin-2 via vasopressin-2 receptor/cAMP/protein kinase A signaling in inner medullary collecting duct cells
Sua Kim, Chor Ho Jo, Gheun‐Ho Kim
Abstract
It is unclear whether antipsychotic drugs can retain water in the kidney in the absence of vasopressin. This study demonstrates that haloperidol, sertraline, and carbamazepine can produce nephrogenic syndrome of inappropriate antidiuresis because they directly upregulate vasopressin-2 receptor and aquaporin-2 (AQP2) via cAMP/PKA signaling. We showed that, in addition to AQP2 trafficking, AQP2 protein abundance was rapidly increased by treatment with antipsychotic drugs in association with dephosphorylation of AQP2 at Ser 261 and accelerated AQP2 transcription.
Topics & Concepts
Aquaporin 2VasopressinDownregulation and upregulationChemistryEndocrinologyInternal medicineArginine vasopressin receptor 2KidneyPharmacologyReceptorCell biologyMedicineBiologyBiochemistryAntagonistWater channelMechanical engineeringEngineeringGeneInletElectrolyte and hormonal disordersIon Transport and Channel RegulationRenal and related cancers